Influence of Population Immunosuppression and Past Vaccination on Smallpox Reemergence

C. Raina MacIntyre; Valentina Costantino; Xin Chen; Eva Segelov; Abrar Ahmad Chughtai; Anthony Kelleher; Mohana Kunasekaran; John Michael Lane

Disclosures

Emerging Infectious Diseases. 2018;24(4):646-653. 

In This Article

Results

Population and Immunity Levels

We examined the population age distributions of New York and Sydney. Sydney has a higher percentage of persons <20 and >55 years of age than New York (Figure 1, panel A), whereas New York has a higher proportion of persons 20–39 years of age than Sydney. We estimated that 4.54% of New York's population and 3.76% of Sydney's population are severely immunocompromised, 14.81% of New York's population and 12.95% of Sydney's population are mildly immunocompromised, 59.14% of New York's population and 72.56% of Sydney's population are healthy unvaccinated, and 21.51% of New York's population and 10.73% of Sydney's population are healthy vaccinated. Similar proportions of the 2 cities' populations (19% in New York and 17% in Sydney) are immunosuppressed (Figure 1, panel B). New York has a higher proportion of the population vaccinated (21%) than Sydney (10%).

Base Case Scenario

We analyzed age-specific infection (Figure 2, panel A) and death (Figure 2, panel B) rates using the base case scenario (medium immunity level) including the immunosuppressed population. Persons 5–19 years of age are at highest risk for smallpox infection in both cities (Figure 2, panel A). Although the proportion of persons infected in both cities is similar among the 0–19-year age groups, ≈25% more persons in New York than Sydney become infected among the 20–39-year age groups.

Figure 2.

Smallpox infection and death rates of population for base case scenario and for scenario including immunosuppression in model, by age group, New York, NY, USA, and Sydney, New South Wales, Australia. Characteristics (e.g., size, age, immunosuppression rates) of populations from 2015 were used. A) Infection rate 50 and 60 days after start of smallpox outbreak; B) cumulative deaths in population 50 and 60 days after start of smallpox outbreak.

Cumulative deaths per 1,000 population increase with age starting with persons >20 years of age (Figure 2, panel B). Deaths peak in the 65–69-year age group in both cities, reaching 1.2 deaths/1,000 population for New York and 0.9 deaths/1,000 population for Sydney 60 days after the start of the outbreak; rates increase again in those >80 years of age. The New York population also has a smaller peak in deaths in the 35–39-year age group. Although the spread of infection is mostly driven by higher contact rates among persons of young age groups, the peaks in death reflect the distribution of the immunosuppressed population (Figure 1, panel B; Figure 2, panel B). The effect of residual immunity is more apparent in New York trends, which show a greater decrease in infections and cumulative deaths in the age groups that were previously vaccinated (40–65 years of age).

Looking at total rates over time, New York (Figure 3, panels A, C) and Sydney (Figure 3, panels B, D) have similar exponential growths of infection rates, with slightly higher trends for New York. The rate of infection reaches 0.094 infected/1,000 population for New York and 0.084 infected/1,000 population for Sydney 50 days after the smallpox introduction and increases to 0.496 infected/1,000 population for New York and 0.452 infected/1,000 population for Sydney by 70 days. The death rates are 0.028 deaths/1,000 population for New York and 0.025 deaths/1,000 population for Sydney after 50 days and reach 0.151 deaths/1,000 population for New York and 0.133 deaths/1,000 population for Sydney by 70 days.

Figure 3.

Smallpox infection and death rates over time considering different immunologic factors included in model, New York, NY, USA, and Sydney, Australia. Characteristics (e.g., size, age, immunosuppression rates) of populations from 2015 were used. A) Rates for New York, considering different levels (none, base case, and high) of residual vaccine immunity with the inclusion of immunosuppressed population. B) Rates for Sydney, considering different levels (none, base case, and high) of residual vaccine immunity with the inclusion of immunosuppressed population. C) Rates for New York, including and excluding immunosuppression with base case level of residual vaccine immunity. D) Rates for Sydney, including and excluding immunosuppression with base case level of residual vaccine immunity.

Residual Immunity Analysis

Infection and death rate estimates for New York, where vaccine coverage is more than double that of Sydney, are more sensitive to assumptions of residual immunity. New York (Figure 3, panel A) has lower rates of infection than Sydney (Figure 3, panel B) only in the scenario of high residual immunity. At day 50 of the outbreak, rates are ≈15% (base case residual immunity) and 31% (high residual immunity) lower in New York and 10% (base case residual immunity) and 17% (high residual immunity) lower in Sydney with residual immunity than without residual immunity. Differences in infection and death rates among different residual immunity assumptions increased with time. Regarding the impact on age-specific rates in New York (Figure 4, panel A) and Sydney (Figure 4, panel B), the assumption of high residual immunity produced lower death rates for the older age groups.

Figure 4.

Smallpox infection and death rates with different levels of residual vaccine immunity including and excluding immunosuppression in model of smallpox transmission, by age group, New York, NY, USA, and Sydney, Australia. Characteristics (e.g., size, age, immunosuppression rates) of populations from 2015 were used. A) New York 50 days after start of smallpox outbreak with no (top), base case (middle), and high (bottom) residual vaccine immunity. B) Sydney 50 days after start of smallpox outbreak with no (top), base case (middle), and high (bottom) residual vaccine immunity.

Immunosuppression Analysis

Infection and death rates increase when including (vs. excluding) immunosuppression parameters in the model; greater differences are seen between New York's infection rates (Figure 3, panel C) and Sydney's infection rates (Figure 3, panel D). The difference in rates increases with time, reaching ≈20% in New York and 18% in Sydney at day 50 from the start of the outbreak and 28% for New York and 25% for Sydney at day 70. Although including immunosuppression estimates into the model produced similarly higher infection rates for each age group (less for the 0–4-year age group), differences in death rates increased with age (Figure 4).

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